Association of sperm-associated antigen 5 and treatment response in patients With estrogen receptor–positive breast cancer

Abdel-Fatah, T.M.A., Thangavelu, P.U., Reid, L.E., McCart Reed, A.E., Saunus, J.M., Duijf, P.H.G., Simpson, P.T., Lakhani, S.R., Ball, G.R. ORCID: 0000-0001-5828-7129, Pongor, L., Gyorffy, B., Moseley, P.M., Green, A.R., Pockley, A.G. ORCID: 0000-0001-9593-6431, Caldas, C., Ellis, I.O. and Chan, S.Y.T., 2020. Association of sperm-associated antigen 5 and treatment response in patients With estrogen receptor–positive breast cancer. JAMA Network Open, 3 (7): e209486. ISSN 2574-3805

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Abstract

Importance: There is no proven test that can guide the optimal treatment, either endocrine therapy or chemotherapy, for estrogen receptor–positive breast cancer.
Objective: To investigate the associations of sperm-associated antigen 5 (SPAG5) transcript and SPAG5 protein expressions with treatment response in systemic therapy for estrogen receptor–positive breast cancer.

Design, Settings, and Participants: This retrospective cohort study included patients with estrogen receptor–positive breast cancer who received 5 years of adjuvant endocrine therapy with or without neoadjuvant anthracycline-based combination chemotherapy (NACT) derived from 11 cohorts from December 1, 1986, to November 28, 2019. The associations of SPAG5 transcript and SPAG5 protein expression with pathological complete response to NACT were evaluated, as was the association of SPAG5 mRNA expression with response to neoadjuvant endocrine therapy. The associations of distal relapse–free survival with SPAG5 transcript or SPAG5 protein expressions were analyzed. Data were analyzed from September 9, 2015, to November 28, 2019.

Main Outcomes and Measures: The primary outcomes were breast cancer–specific survival, distal relapse–free survival, pathological complete response, and clinical response. Outcomes were examined using Kaplan-Meier, multivariable logistic, and Cox regression models.

Results: This study included 12 720 women aged 24 to 78 years (mean [SD] age, 58.46 [12.45] years) with estrogen receptor–positive breast cancer, including 1073 women with SPAG5 transcript expression and 361 women with SPAG5 protein expression of locally advanced disease stage IIA through IIIC. Women with SPAG5 transcript and SPAG5 protein expressions achieved higher pathological complete response compared with those without SPAG5 transcript or SPAG5 protein expressions (transcript: odds ratio, 2.45 [95% CI, 1.71-3.51]; P < .001; protein: odds ratio, 7.32 [95% CI, 3.33-16.22]; P < .001). Adding adjuvant anthracycline chemotherapy to adjuvant endocrine therapy for SPAG5 mRNA expression in estrogen receptor–positive breast cancer was associated with prolonged 5-year distal relapse–free survival in patients without lymph node involvement (hazard ratio, 0.34 [95% CI, 0.14-0.87]; P = .03) and patients with lymph node involvement (hazard ratio, 0.35 [95% CI, 0.18-0.68]; P = .002) compared with receiving 5-year endocrine therapy alone. Mean (SD) SPAG5 transcript was found to be downregulated after 2 weeks of neoadjuvant endocrine therapy compared with pretreatment levels in 68 of 92 patients (74%) (0.23 [0.18] vs 0.34 [0.24]; P < .001).

Conclusions and Relevance: These findings suggest that SPAG5 transcript and SPAG5 protein expressions could be used to guide the optimal therapies for estrogen receptor–positive breast cancer. Retrospective and prospective clinical trials are warranted.

Item Type: Journal article
Publication Title: JAMA Network Open
Creators: Abdel-Fatah, T.M.A., Thangavelu, P.U., Reid, L.E., McCart Reed, A.E., Saunus, J.M., Duijf, P.H.G., Simpson, P.T., Lakhani, S.R., Ball, G.R., Pongor, L., Gyorffy, B., Moseley, P.M., Green, A.R., Pockley, A.G., Caldas, C., Ellis, I.O. and Chan, S.Y.T.
Publisher: American Medical Association (AMA)
Date: 7 July 2020
Volume: 3
Number: 7
ISSN: 2574-3805
Identifiers:
NumberType
10.1001/jamanetworkopen.2020.9486DOI
1342284Other
Rights: Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Abdel-Fatah TMA et al. JAMA Network Open.
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 09 Jul 2020 07:40
Last Modified: 07 Oct 2020 07:26
URI: http://irep.ntu.ac.uk/id/eprint/40193

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